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Biomedical subjects

L Lasagna

Publications and source records attributed to L Lasagna.

At least 73 records · Page 4Linked to original sources
PubMed1986

The management of pain.

Pain is a complex phenomenon involving both neurophysiological and psychological components. Pathophysiological mechanisms involve neural pathways, and a variety of pain-producing substances and modulating mechanisms. These include acetylcholine, serotonin, histamine, bradykinin, prostaglandins, substance P, somatostatin, cholecystokinin, vasoactive intestinal polypeptide, noradrenaline and endogenous opioid peptides. In assessing patients with pain, it is essential to evaluate the cause of the pain, its severity, type, location, duration, quality, and response to therapies, among other factors. The measurement of pain is dependent on subjective responses, which are evaluated by methods which have been well developed over the last three decades. Alleviation of pain by non-drug treatments must be considered as well as use of pharmacological treatments. These include psychological support, placebos, relaxation training, biofeedback, hypnosis, heat, cold, physical supports and surgery. Oral drugs are generally preferable to parenteral drugs, as are drugs with few side effects and low addictive liability. Both overtreatment and undertreatment are to be avoided. Patients can be expected to differ in their needs and responses, and economic considerations ought not be ignored. Newer approaches to pain management include self-administration of parenteral drugs, the search for new types of analgesics and appreciation of the relationship between age, sex, race, etc. and the response to analgesics. Tricyclic antidepressants, phenothiazines and the new non-steroidal anti-inflammatory drugs have pointed the way to possible improvements in our ability to tailor specific drugs to the needs of individual patients.

Humans↗
PubMed1986

Bioavailability and pharmacological effects of two slow-release theophylline preparations: intrasubject tablet-to-tablet variability.

The bioavailability and pharmacological effects of slow-release preparations oxtriphylline (Choledyl SA) and anhydrous theophylline (Theo-Dur) were compared in a single-blind, randomized, crossover study in 10 normal men. Subjects were administered three doses from the same lot of each preparation at weekly intervals. Plasma concentration of theophylline was measured at timed intervals for 33 hr by high-pressure liquid chromatography. Pharmacokinetic analysis showed that Choledyl SA peaked earlier (4.7 +/- 1.0 hr) than did Theo-Dur (9.6 +/- 8.2 hr), with higher peak concentrations, 6.4 +/- 0.7 micrograms/ml versus 4.1 +/- 0.5 micrograms/ml for Theo-Dur, and greater are under the curve, 102.4 +/- 15.7 micrograms/ml X hr versus 75.3 +/- 9.1 micrograms/ml X hr for Theo-Dur. 88% absorption was achieved in 6 hr with Choledyl SA versus 10 hr with Theo-Dur. Wide intra- and intersubject variations were observed with both preparations. Likewise, variable effects on systolic and diastolic blood pressure and pulse were observed with both preparations. The effects of both theophylline preparations on urine flow, osmolar clearance, and glomerular filtration rate were compared. Osmotic diuresis without detectable changes in the glomerular filtration rate was observed in subjects who received Choledyl SA versus Theo-Dur. Differences in the bioavailability and renal effects were observed between Choledyl SA and Theo-Dur. Wide intra- and intersubject tablet-to-tablet variability were observed with both preparations.

Adolescent↗
PubMed1985

From DNA to NDA--the impact of recombinant DNA technology on new drug development.

Man's long-standing efforts to alter living things through genetic manipulation have become reality. Recent advances in recombinant DNA technology have the potential to alter the drug-development process profoundly. The pharmaceutical industry has had to adjust its research efforts and develop new state-of-the-art laboratories. In addition to the standard biological and in vivo assays, many new tests are required, e.g., amino acid sequencing, high-pressure liquid chromatography, and radioimmunoassays. Academic researchers have played a vital role in developing the new biotechnology, supplying most of the basic scientific knowledge and the initial supply of the scientific work force. The recent shifting of support for scientific training from the government to the pharmaceutical industry has resulted in unprecedented academe-industry relationships. Universities now stand to profit significantly from patent rights resulting from biotechnology research efforts. While the advances in biotechnology have had considerable impact on the pharmaceutical industry and academia, they have thus far had only a minor impact on the regulatory process. To date, the preferred regulatory path appears to be modification of existing procedures through the issuance of guidelines, which can be updated as knowledge increases.

Academies and Institutes↗
PubMed1985

The interaction between bleomycin and radiation on cell survival and DNA damage in mammalian cell cultures.

Chinese hamster ovary (CHO) cells were exposed to various concentrations of bleomycin (BLM) for 0.5, 1, 2, 4, 6, or 24 hours, followed with graded doses (0 to 800 rad) or radiation. The response to this chemotherapy-radiation combination treatment was measured by cell survival studies and DNA damage as determined by alkaline elution assay. Isobolograms for 1 and 2 log cell kills showed that cytotoxicity from BLM and from radiation were additive at 4, 15 and 75 milliunit/ml (mu/ml) for 1 or 4 hour exposure. When the exposure time of BLM was extended to 24 hours, slightly supraadditivity of lethality was found for the combination treatment with pharmacologically pertinent concentrations of 4 or 15 mu/ml. Therefore 4, 15 and 75 mu/ml concentrations of BLM all interacted positively with all doses of radiation to give enhanced cell kill. The alkaline elution patterns from the BLM-radiation combination also showed an enhancing effect on single strand breaks of DNA from treated cells. A human oat cell carcinoma cell line (MEMAR cells) was also studied and found to be more sensitive to BLM than were CHO cells.

Animals↗
PubMed1985

Oral ciramadol in the treatment of postoperative pain.

The efficacy and safety of single oral 15, 30, and 60 mg doses of ciramadol, an investigational agonist/antagonist analgesic, were studied in a postoperative pain model and compared with aspirin, 325 and 650 mg. Two visual analog pain assessment scales were also compared. Results showed that a pain relief score of moderate or better was reported at some time during the 6-hour observation period by 76% of the patients who took 15 mg ciramadol, by 60% of those who took 30 mg ciramadol, by 59% of those who took 60 mg ciramadol, and by 38% and 92% of the patients who took the low and high doses of aspirin, respectively. From 1 to 4 hours after drug dosing, 15 mg ciramadol generally produced higher scores, indicative of greater pain relief, on the three pain intensity efficacy scales used (verbal, linear analog, and curvilinear analog) than did the other two ciramadol doses, but these differences were generally not significant. The differences between 15 mg ciramadol and 650 mg aspirin were generally not significant, although the higher aspirin dose had some advantages over 15 mg ciramadol. The most frequently reported adverse effect was dizziness/vertigo in 22% of patients taking 60 mg ciramadol, in 17% of those taking 30 mg ciramadol, in 13% of those taking 15 mg ciramadol, in 4% of those taking high aspirin doses, and in none of those who received the low aspirin doses. The correlation coefficient for the linear and curvilinear pain analog intensity scales was 0.955, indicating a highly significant correlation (P less than 0.001).

Adolescent↗
PubMed1984

Drug discontinuations in the United Kingdom and the United States, 1964 to 1983: issues of safety.

Since the modern era of drug regulation began in the early 1960s, fewer new drugs have been approved for marketing in the United States than in the United Kingdom. We examined whether information can be obtained about the relative safety of higher and lower introductory rate policies by comparing each country's record of drugs that have been discontinued (removed from the market, withdrawn, or whose licenses were allowed to lapse) while a question of safety existed. We have compiled a list of both older (approved before 1964) and newer (approved in 1964 or later) chemical entities discontinued in the last two decades. With the aforementioned broad criteria to define "discontinuation," and to assess whether a question of safety was involved, our study showed that a total of 24 chemical entities have been discontinued in the United States or the United Kingdom. Nearly half (10 drugs) were products that had been approved in both countries, while the remainder (drugs that had been exclusively available in one country or the other) consisted of four drugs in the United States and 10 in the United Kingdom. Among the drugs introduced during the last two decades, five have been discontinued in the United States and eight in the United Kingdom. Each country's record of discontinuations has been remarkably similar for drugs introduced after 1974: Four have been discontinued in the United States and three in the United Kingdom. Since drugs discontinued while a safety question existed represent only 2% of the new chemical entities introduced, it appears that drugs that reach the market under the prevailing regulatory systems are seldom associated with unacceptable toxicity.

Animals↗
PubMed1983

Analysis of narcotic analgesic usage in the treatment of postoperative pain.

We reviewed 526 medical records of surgical patients and interviewed 81 of these patients. We also sent questionnaires to house staff (57 of 97 responded) and nurses (70 of 142 responded) involved in the care of these patients. A substantial number of patients suffered at least moderate pain during the postoperative period despite analgesic medication. Patients received 70% of the maximal ordered analgesic dose in the first 24 hours. Physicians prescribed drugs in doses that were often inadequate and to be given at inflexible intervals. The optimal doses and duration of action of meperidine, as judged by the house staff and nurses, did not agree with the accepted pharmacologic profile of this drug.

Acute Disease↗
PubMed1983

Studies with different types of visual analog scales for measurement of pain.

We compared the sensitivity of different types of visual analog scales and of descriptive pain terms in healthy volunteers and in postoperative patients. One hundred and seven volunteers marked visual analog scales according to their perception of the descriptive pain terms--little, mild, some, moderate, severe, agonizing. Individual variation in values and preferences between the five following five different visual analog scales were analyzed: 10-cm linear horizontal and vertical scales, a curvilinear scale, and graded horizontal and curvilinear scales. Significantly more volunteers preferred the horizontal scale with gradations. Scores for the vertical linear scale had the greatest coefficient of variation and were least normally distributed. The majority of volunteers considered the phrase "agonizing pain" the best term defining the extreme limit of pain (X2(12) = 41.8, P less than 0.001). There were significant changes in the values of pain intensity measured on visual analog scales by patients using the same descriptive pain term on successive observations. However, the patients' values for pain terms in the preoperative pain-free state were not significantly different from those during postoperative pain. We conclude that graded linear horizontal scales are both more reliable and preferred by participants and that visual analog scales give a more sensitive and accurate representation of pain intensity than do descriptive pain scales.

Adolescent↗
PubMed1983

Evaluation of current clinical trial methodology in analgesimetry based on experts' opinions and analysis of several analgesic studies.

There is general agreement that the controlled clinical trial is the best method for analgesic evaluation. Current practice in clinical analgesimetry, however, varies considerably with regard to design, measurement of pain, and statistical analysis. We attempted to assess the degree of this diversity by a questionnaire survey of a sample of investigators who are currently conducting clinical pain studies. To examine how various statistical methods perform in practice, we reanalyzed data from four of our published analgesic studies using a number of standard methods.

Analgesia↗
PubMed1983

A comparison of drug product information in four national compendia.

Four widely used compendia of prescribing information have been received to examine the way in which some drug companies recommend uses for several anti-inflammatory products and describe the major dangers in their use. The Physician's Desk Reference (PDR) cites the greatest absolute number of indications for steroids with systemic action, as well as the greatest number of contraindications, warnings and precautions, and adverse effects. The total number of precautions appearing in the PDR is three times the mean for the other compendia, and the number of adverse effects is four times the mean of the others. Together, these other compendia contain 70.5% of the number of words in the PDR. The PDR contains statements that are strongly directive for the physician and that do not appear in the other compendia. Regulatory and social differences may at least partially explain these discrepancies.

Administration, Topical↗
PubMed1983

New drug development during and after a period of regulatory change: clinical research activity of major United States pharmaceutical firms, 1958 to 1979.

The 1962 drug amendments fundamentally changed the way in which U.S. pharmaceutical firms could test new drugs in man and receive New Drug Application (NDA) approval. Although it is well known that the amendments and associated events caused a profound decline in the annual number of new drugs receiving NDA approval, the amendments' effects on clinical research into new chemical entities (NCEs) have not been investigated because data were unavailable. To study this we requested drug development information dating back to 1958 from most major United States-owned pharmaceutical firms and obtained complete responses from nine. The results showed that the introduction rate of NCEs into human testing dropped sharply in the early 1960s and declined substantially thereafter. The number of NCEs entering human testing fell from a mean of 89 a year in 1958-1962, to 35 a year in 1963-1972 (a reduction of 61%), and to 17 a year in the last 5 years of the survey, 1975-1979--an overall reduction of 81%. The number of NDA approvals received by these firms fell sharply by 49% in the early 1960s and more slowly for 10 years thereafter, from the mid-1960s to the mid-1970s. In the case of self-originated NCEs, the size of this later fall was 71%. Causes of these changes in NCE flow include the amendments and the events that prompted them; changes in scientific philosophy, standards, and state of the art; and economic factors.

Drug Evaluation↗